Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren’s syndrome
Joanna Groom, … , Charles R. Mackay, Fabienne Mackay
Joanna Groom, … , Charles R. Mackay, Fabienne Mackay
Published January 1, 2002
Citation Information: J Clin Invest. 2002;109(1):59-68. https://doi.org/10.1172/JCI14121.
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Article

Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren’s syndrome

Abstract

BAFF (BLyS, TALL-1, THANK, zTNF4) is a member of the TNF superfamily that specifically regulates B lymphocyte proliferation and survival. Mice transgenic (Tg) for BAFF develop an autoimmune condition similar to systemic lupus erythematosus. We now demonstrate that BAFF Tg mice, as they age, develop a secondary pathology reminiscent of Sjögren’s syndrome (SS), which is manifested by severe sialadenitis, decreased saliva production, and destruction of submaxillary glands. In humans, SS also correlates with elevated levels of circulating BAFF, as well as a dramatic upregulation of BAFF expression in inflamed salivary glands. A likely explanation for disease in BAFF Tg mice is excessive survival signals to autoreactive B cells, possibly as they pass through a critical tolerance checkpoint while maturing in the spleen. The marginal zone (MZ) B cell compartment, one of the enlarged B cell subsets in the spleen of BAFF Tg mice, is a potential reservoir of autoreactive B cells. Interestingly, B cells with an MZ-like phenotype infiltrate the salivary glands of BAFF Tg mice, suggesting that cells of this compartment potentially participate in tissue damage in SS and possibly other autoimmune diseases. We conclude that altered B cell differentiation and tolerance induced by excess BAFF may be central to SS pathogenesis.

Authors

Joanna Groom, Susan L. Kalled, Anne H. Cutler, Carl Olson, Stephen A. Woodcock, Pascal Schneider, Jurg Tschopp, Teresa G. Cachero, Marcel Batten, Julie Wheway, Davide Mauri, Dana Cavill, Tom P. Gordon, Charles R. Mackay, Fabienne Mackay

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Figure 1

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Enlarged and inflamed salivary glands in BAFF Tg mice. (a) Mice 15–17 mo...
Enlarged and inflamed salivary glands in BAFF Tg mice. (a) Mice 15–17 months old (four control littermates and four BAFF Tg mice) were sacrificed the same day for organ collection. Both right and left submaxillary glands were collected and weighed. The data shows the combined weight (mean ± SD) of both glands. These results are representative of at least four separate groups of dissected age-matched animals. (b) Paraffin sections of submaxillary glands from a control littermate (left panel) and two BAFF Tg mice (middle and right panels) were stained with hematoxylin and eosin. Arrows indicate ducts and acinar cells in the left and right panels. The arrow in the middle panel shows acinar destruction. Asterisks indicate periductal infiltrates (foci). Magnification: ×100. (c) Paraffin sections of submaxillary glands from seven control mice and 22 BAFF Tg mice (12–17 months old) were prepared as shown in b and scored for disease as described in Methods. Bars indicate the mean disease score for each group. *P < 0.05, **P < 0.03.